Inflammation in Arteries vs. Lymph Nodes

As mentioned earlier in this issue of TreatmentUpdate, chronic HIV infection is associated with excessive levels of inflammation and activation of the immune system. Some of this is reduced when people initiate HIV therapy (ART) and achieve and maintain very low levels of virus in their blood (these low levels are commonly called "undetectable"). However, researchers are concerned that the residual inflammation that persists in ART users could cause health problems over the long term.

Researchers in San Francisco have conducted an intensive study of inflammation in the arteries and nearby lymph nodes of 74 men, some of whom were HIV positive and using ART. The researchers found that inflammation in the arteries of HIV-positive people was "modestly increased" and linked to having higher levels of proteins associated with inflammation, such as IL-6 (interleukin-6) and CRP (C-reactive protein). Furthermore, among HIV-positive people, the level of inflammation in the lymph nodes was generally higher than in the arteries. This finding prompted the researchers to conclude that inflammation in the arteries and lymph nodes "is not closely linked." Another finding from this study is that the factors that drive inflammation in the arteries are somewhat different from those that drive inflammation in the lymph nodes. The researchers suggest that therapies that reduce HIV "disease activity" may not reduce inflammation in the arteries or the consequences of such inflammation, namely heart attacks and strokes.

A Note About Scans

In the present study, the research team used a technique called FDG PET/CT scans. In these scans, a small amount of radioactive sugar (FDG) is given to the person via intravenous infusion. Researchers then wait some time for this sugar to be taken up by active tissues; in this case, in the lymph nodes and arteries, where inflammation was taking place. The PET (positron emission tomography) scan detects the radioactive material and its location, while the CT (computer tomography) scan helps to form detailed images of the tissues where the FDG has concentrated. FDG usually concentrates in cells/tissues where there is a very high level of inflammation.

Study Details

Participants had a similar profile upon entering the study (regardless of HIV infection): They were in their early 50s and the proportion of HIV-positive and HIV-negative people with risk factors for cardiovascular disease was similar. Some HIV-positive participants were taking ART and had undetectable viral loads.

Results

Inflammation in the lymph nodes was greater among HIV-positive participants. Among HIV-positive people, inflammation in the lymph nodes was greatest among those who were taking ART and who did not have an undetectable viral load. In a subset of participants, researchers were able to assess the spleen (a major organ of the immune system) and found that levels of inflammation there were similar to levels of inflammation in the lymph nodes.

Links to Inflammation in the Lymph Nodes

Among HIV-positive people, high levels of inflammation in the lymph nodes were associated with the following blood test results:

a high viral load

higher numbers of CD8+ cells

a lower CD4/CD8 ratio

The researchers did not find any links between these three factors and inflammation in the arteries.

Links to Inflammation in the Arteries

Levels of IL-6 and CRP in the blood were linked to inflammation in the arteries. (Elevated levels of IL-6 were also linked to inflammation in the lymph nodes.) Inflammation in the arteries was also linked to a group of the immune system's cells called monocytes (in their mature form these are called macrophages).

What the Findings Mean

The researchers think that it is likely that the drivers of immune activation and inflammation in the arteries are different from those in the lymph nodes. These findings are supported by another U.S. study.

Taking the findings from both studies into account, it is very likely that ART alone will be insufficient to significantly reduce inflammation in the arteries.

Some of the researchers from this study are now exploring the impact of the antibody canakinumab on arterial inflammation in people with HIV. Their findings are reported later in this issue of TreatmentUpdate.

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